Staff
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ProfessorJunko MatsudaJunko Matsuda
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Assistant ProfessorYuta IshizukaYuta Ishizuka
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InstructorTakashi WatanabeTakashi Watanabe
Glycosphingolipids (GSLs) are amphipathic membrane lipids present in the outer leaflet of the plasma membrane of all vertebrate cells. GSLs consist of sugar chain and ceramide moieties, each with characteristic structural diversity that is strictly maintained by the metabolic balance of synthesis and degradation. Defective lysosomal degradation of GSLs due to a lack of either a specific lysosomal glycosidase or an activator protein causes sphingolipidoses, most of which show serious neurological symptoms in childhood. Several disorders due to the defect of GSLs synthetic metabolism have also been found. We are interested in solving the mystery of the Sphinx, which is in fact the origin of the word 'Sphingolipid' focusing on the structure and metabolism of these lipids and the diseases caused by metabolic defects involving them. Our current interests are in three main areas:
- Biological significance of structural diversity of ceramide moiety
Ceramide, a hydrophobic portion of GSL, is composed of sphingoid base and fatty acid. Each part has strictly regulated structural diversity by cell type, organ, tissue, and developmental stage. In our studies, we are aiming to elucidate the biological significance of structural diversity of ceramide moiety using genetically modified mouse models.
- Pathophysiology and therapy in sphingolipidoses, focusing on Krabbe’s disease
Krabbe's disease is an inherited demyelinating disease caused by a deficiency of the lysosomal enzyme, galactosylceramide-β-galactosidase (GALC). In this area, we are aiming to develop new therapeutic approaches for Krabbe’s disease.
- Biological and pathophysiological function of prosaposin and saposins in the nervous system, sphingolipidoses, and the more common neurodegenerative diseases
Saposins (SAPs)-A, B, C, and D are hydrophobic glycoproteins derived from the precursor protein, prosaposin (PSAP). They are essential for the hydrolysis of GSLs in lysosomes. We have developed SAP-A, SAP-C, and SAP-D specific deficient mice and are aiming to elucidate the biological and pathophysiological function of PSAP and SAPs in the nervous system, sphingolipidoses, and the more common neurodegenerative diseases.